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FIGURE 9-20 Synteny in the mouse and human genomes. Large segments of the mouse and human genomes have closely related genes aligned in the same order on chromosomes, a relationship called synteny. This diagram shows segments of human chromosome 9 and mouse chromosome 2. The genes in these segments exhibit a very high degree of homology as well as the same gene order. The different lettering schemes for the gene names reflect different naming conventions in the two organisms.

To further the assignment of function based on structural relationships, a large-scale structural pro-teomics project has been initiated. The goal is to crystallize and determine the structure of as many proteins and protein domains as possible, in many cases with little or no existing information about protein function. The project has been assisted by the automation of some of the tedious steps of protein crystallization (see Box 4-4). As these structures are revealed, they will be made available in the structural databases described in Chapter 4. The effort should help define the extent of variation in structural motifs. When a newly discovered protein is found to have structural folds that are clearly related to motifs with known functions in the databases, this information can suggest a molecular function for the protein.

Cellular Expression Patterns Can Reveal the Cellular Function of a Gene

In every newly sequenced genome, researchers find genes that encode proteins with no evident structural relationships to known genes or proteins. In these cases, other approaches must be used to generate information about gene function. Determining which tissues a gene is expressed in, or what circumstances trigger the appearance of the gene product, can provide valuable clues. Many different approaches have been developed to study these patterns.

Two-Dimensional Gel Electrophoresis As shown in Figure 3-22, two-dimensional gel electrophoresis allows the separation and display of up to 1,000 different proteins on a single gel. Mass spectrometry (see Box 3-2) can then be used to partially sequence individual protein spots and assign each to a gene. The appearance and nonappearance (or disappearance) of particular protein spots in samples from different tissues, from similar tissues at different stages of development, or from tissues treated in ways that simulate a variety of biological conditions can help define cellular function.

DNA Microarrays Major refinements of the technology underlying DNA libraries, PCR, and hybridization have come together in the development of DNA microar-rays (sometimes called DNA chips), which allow the rapid and simultaneous screening of many thousands of genes. DNA segments from known genes, a few dozen to hundreds of nucleotides long, are amplified by PCR and placed on a solid surface, using robotic devices that accurately deposit nanoliter quantities of DNA solution. Many thousands of such spots are deposited in a predesigned array on a surface area of just a few square centimeters. An alternative strategy is to synthesize DNA directly on the solid surface, using photolithography (Fig. 9-21). Once the chip is constructed, it can be probed with mRNAs or cDNAs from a particular cell type

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